Effect of exercise during pregnancy on offspring development through ameliorating high glucose and hypoxia in gestational diabetes mellitus

BACKGROUND Gestational diabetes mellitus(GDM)women require prenatal care to minimize short-and long-term complications.The mechanism by which exercise during pregnancy affects organ development and whether glucose transporter(GLUT)1 plays a role in GDM offspring organ development remains unknown.AIM To determine the effect of exercise during pregnancy on the cardiac,hepatic and renal development of GDM mother’s offspring.METHODS Placenta samples were collected from humans and mice.GDM mouse models were created using streptozotocin along with a GDM with exercise group.The hearts,livers and kidneys of 3-and 8-week-old offspring were collected for body composition analysis and staining.The effects of high glucose levels and hypoxia were investigated using HTR8/SVneo.Transwell and wound-healing assays were performed to assess cell migration.Immunofluorescence accompanied with TUNEL and Ki67 staining was used to explore apoptosis and proliferation.RESULTS Exercise during pregnancy downregulated the GLUT1 and hypoxia inducible factor-1αexpression in placenta from individuals with GDM.Cobalt chloride induced hypoxia and high glucose levels also significantly decreased migration and apoptosis of HTR8/SVneo cells.In addition,exercise reduced inflammatory cell infiltration in the liver and decreased the tubular vacuolar area in the kidneys of offspring.CONCLUSION GDM affects the growth and development of organs in offspring.Exercise during pregnancy can reverse adverse effects of GDM on the development of the heart,liver,and kidney in offspring.

New aspects of a small GTPase RAB35 in brain development and function

In eukaryotic cells,organelles in the secretory,lysosomal,and endocytic pathways actively exchange biological materials with each other through intracellular membrane trafficking,which is the process of transporting the cargo of proteins,lipids,and other molecules to appropriate compartments via transport vesicles or intermediates.These processes are strictly regulated by various small GTPases such as the RAS-like in rat brain(RAB)protein family,which is the largest subfamily of the RAS superfamily.Dysfunction of membrane trafficking affects tissue homeostasis and leads to a wide range of diseases,including neurological disorders and neurodegenerative diseases.Therefore,it is important to understand the physiological and pathological roles of RAB proteins in brain function.RAB35,a member of the RAB family,is an evolutionarily conserved protein in metazoans.A wide range of studies using cultured mammalian cells and model organisms have revealed that RAB35 mediates various processes such as cytokinesis,endocytic recycling,actin bundling,and cell migration.RAB35 is also involved in neurite outgrowth and turnover of synaptic vesicles.We generated brain-specific Rab35 knockout mice to study the physiological roles of RAB35 in brain development and function.These mice exhibited defects in anxiety-related behaviors and spatial memory.Strikingly,RAB35 is required for the precise positioning of pyramidal neurons during hippocampal development,and thereby for normal hippocampal lamination.In contrast,layer formation in the cerebral cortex occurred superficially,even in the absence of RAB35,suggesting a predominant role for RAB35 in hippocampal development rather than in cerebral cortex development.Recent studies have suggested an association between RAB35 and neurodegenerative diseases,including Parkinson's disease and Alzheimer's disease.In this review,we provide an overview of the current understanding of subcellular functions of RAB35.We also provide insights into the physiological role of RAB35 in mammalian brain development and function,and discuss the involvement of RAB35 dysfunction in neurodegenerative diseases.

Establishment of human cerebral organoid systems to model early neural development and assess the central neurotoxicity of environmental toxins

Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and disease.To enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture.This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid system.This cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology testing.As a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins.Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature differentiation.Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic locations.The convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.

Postnatal development of rat retina:a continuous observation and comparison between the organotypic retinal explant model and in vivo development

The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures.However,the lack of systematic and continuous comparison between in vivo retinal development and the organotypic retinal explant culture makes this model controversial in postnatal retinal development studies.Thus,we aimed to verify the feasibility of using this model for postnatal retinal development studies by comparing it with the in vivo retina.In this study,we showed that postnatal retinal explants undergo normal development,and exhibit a consistent structure and timeline with retinas in vivo.Initially,we used SOX2 and PAX6 immunostaining to identify retinal progenitor cells.We then examined cell proliferation and migration by immunostaining with Ki-67 and doublecortin,respectively.Ki-67-and doublecortin-positive cells decreased in both in vivo and explants during postnatal retinogenesis,and exhibited a high degree of similarity in abundance and distribution between groups.Additionally,we used Ceh-10 homeodomain-containing homolog,glutamate-ammonia ligase(glutamine synthetase),neuronal nuclei,and ionized calcium-binding adapter molecule 1 immunostaining to examine the emergence of bipolar cells,Müller glia,mature neurons,and microglia,respectively.The timing and spatial patterns of the emergence of these cell types were remarkably consistent between in vivo and explant retinas.Our study showed that the organotypic retinal explant culture model had a high degree of consistency with the progression of in vivo early postnatal retina development.The findings confirm the accuracy and credibility of this model and support its use for long-term,systematic,and continuous observation.

Modified halloysite nanotubes reduce the toxic effects of zearalenone in gestating sows on growth and muscle development of their offsprings

Background： Zearalenone （ZEN） is an estrogenic mycotoxin that is primarily produced by Fusarium fungi and has been proven to affect the reproductive capacity of many species to varying degrees. The present experiment was designed to study the maternal persistent effects of zearalenone toxicity in gestating sows on growth and muscle development of their offsprings, and the alleviation of zearalenone toxicity by modified halloysite nanotubes （MHNTs）. Methods： Eighteen sows were fed with one of three dietary treatments that included the following： （1） a control diet, （2） a contaminated grain diet （with 50 % moldy corn, 2.77 mg/kg ZEN）, and （3） a contaminated grain diet （with 50 % moldy corn, 2.76 mg/kg ZEN） ＋ 1% MHNTs. Each sow was exclusively fed its experimental diets from 35 to 70 d of gestation at a total of 2 kg daily. Muscle samples were collected from six piglets per treatment at birth, weaning and finishing. Results： The results showed that feeding the sows with the ZEN-contaminated diets from 35 to 70 d of gestation decreased the ADG, ADFI and G：F of their offsprings （P 〈 0.05）. The muscle fiber numbers in the newborn, weaning and growing-finishing pigs and the muscle fiber diameters at birth and weaning were also decreased by maternal ZEN exposure （P 〈 0.05）. The expressions of IGF-I, IGF-II, Myf-5 and Mstn at birth and IGF-II, Pax7, Myf-5 and MyoD1 at weaning were altered by feeding gestating sows with ZEN-contaminated diets （P 〈 0.05）. The MHNTs reduced most of the ZEN-induced toxic effects： the ADG and ADFI on growth performance, the muscle fiber numbers at weaning and finishing and the muscle fiber diameters at weaning （P 〈 0.05）. The expression levels of IGF-II and Mstn in newborn piglets and IGF-II and Myf-5 in weaning piglets were also prevented by adding 1% MHNTs （P 〈 0.05）. Conclusions： The present study demonstrated that the offsprings of sows fed with ZEN-contaminated diets from 35 to 70 day of gestation exhibited weakening on growth performance, physiological changes in their muscle fibers and alterations of mRNA expression in their muscle tissues, and also indicated that MHNTs prevented most of the ZEN- induced weakening in the muscle tissues.

Association between Pre-pregnancy Body Mass Index and Offspring Neuropsychological Development from 1 to 24 Months of Age: A Birth Cohort Study in China

Objective To explore the interactions between pre-pregnancy body mass index(BMI) and age on offspring neuropsychological development from 1 to 24 months in China.Methods In this birth cohort study, a total of 2,253 mother-child pairs were enrolled in Tianjin, China,between July 2015 and May 2018. The China Developmental Scale for Children was used to assess developmental quotient(DQ) of children aged from 1 to 24 months.Results Mixed-models analysis revealed significant age × pre-pregnancy BMI interactions for total DQ and five neurobehavioral domains(gross motor, fine motor, adaptive, language, and social;P < 0.001).Age × pre-pregnancy BMI ≥ 25 kg/m^2 was associated with a negative effect on total DQ and five neurobehavioral domains, as compared to pre-pregnancy BMI < 25 kg/m^2(P < 0.01). Multiple comparisons showed pre-pregnancy BMI ≥ 25 kg/m^2 of mothers had a positive effect on child total DQ at the age of 1 month but a negative effect at 24 months(P < 0.05).Conclusions This study supported the age × pre-pregnancy BMI interaction on offspring neuropsychological development. It also revealed a short-term positive impact of high pre-pregnancy BMI on neuropsychological development at 1 month of age, but a long-term negative effect(from 1 to24 months).

Epigenetic modifications of placenta in women with gestational diabetes mellitus and their offspring

Gestational diabetes mellitus(GDM)is a pregnancy-related complication characterized by abnormal glucose metabolism in pregnant women and has an important impact on fetal development.As a bridge between the mother and the fetus,the placenta has nutrient transport functions,endocrine functions,etc.,and can regulate placental nutrient transport and fetal growth and development according to maternal metabolic status.Only by means of placental transmission can changes in maternal hyperglycemia affect the fetus.There are many reports on the placental pathophysiological changes associated with GDM,the impacts of GDM on the growth and development of offspring,and the prevalence of GDM in offspring after birth.Placental epigenetic changes in GDM are involved in the programming of fetal development and are involved in the pathogenesis of later chronic diseases.This paper summarizes the effects of changes in placental nutrient transport function and hormone secretion levels due to maternal hyperglycemia and hyperinsulinemia on the development of offspring as well as the participation of changes in placental epigenetic modifications due to maternal hyperglycemia in intrauterine fetal programming to promote a comprehensive understanding of the impacts of placental epigenetic modifications on the development of offspring from patients with GDM.

The Development of Metabolic Derangement in Male Offspring after Perinatal Exposure to Di-(2-Ethylhexyl) Phthalate

The prevalence of obesity and type 2 diabetes mellitus（T2DM）has been increasing throughout the world over the past 20 years.Environmental chemicals known to regulate the endocrine system have been considered as a risk factor for the development of metabolic diseases.Several people are exposed to environmental chemicals during their lives.

Poor maternal nutrition inhibits muscle development in ovine offspring

Background： Maternal over and restricted nutrition has negative consequences on the muscle of offspring by reducing muscle fiber number and altering regulators of muscle growth. To determine if over and restricted maternal nutrition affected muscle growth and gene fed 60%, 100% or 140% of National Research Council and protein expression in offspring, 36 pregnant ewes were requirements from d 31 ＋ 1,3 of gestation until parturition. Lambs from control-fed （CON）, restricted-fed （RES） or over-fed （OVER） ewes were necropsied within 1 d of birth （n = 18） or maintained on a control diet for 3 mo （n = ] 5）. Semitendinosus muscle was collected for immunohistochemistry, and protein and gene expression analysis. Results： Compared with CON, muscle fiber cross-sectional area （CSA） increased in RES （58%） and OVER （47%） lambs at 1 d of age （P〈 0.01）; however at 3 mo, CSA decreased 15% and 17% compared with CON, respectively （P 〈 0.01）. Compared with CON, muscle lipid content was increased in OVER （212.4%） and RES （92.5%） at d 1 （P 〈 0.0001）. Muscle lipid content was increased 36.1% in OVER and decreased 23.6% in RES compared with CON at 3 mo （P 〈 0.0001）. At d 1, myostatin mRNA abundance in whole muscle tended to be greater in OVER （P = 0.07） than CON. Follistatin mRNA abundance increased in OVER （P = 0.04） and tended to increase in RES （P = 0.06） compared with CON at d 1. However, there was no difference in myostatin or follistatin protein expression （P 〉 0.3）. Phosphorylated Akt （ser473） was increased in RES at 3 mo compared with CON （P = 0.006）. Conclusions： In conclusion, maternal over and restricted nutrient intake alters muscle lipid content and growth of offspring, possibly through altered gene and protein expression.

GAMYB transcription factor LoMYB65 from lily plays a vital role in pollen development

Lily(Lilium spp.)is an important horticultural crop,but its use is limited due to serious pollen contamination problems.There are many studies on pollen development in model plants,but few on flower crops such as lilies.Gibberellin(GA)is a large class of hormones and plays an important role in plant vegetative growth and reproductive development.GAMYB is a group of the R2R3-MYB family upregulated by gibberellin,and plays an important role in anther development.Here,we isolated a novel GAMYB,named LoMYB65,from lily,which was closely related to the AtMYB65 and AtMYB33 in Arabidopsis.Fluorescence quantitative PCR results showed that LoMYB65 was mainly expressed in lily anthers.LoMYB65 could be activated by 288μmol·L^(-1)GA3treatment and the LoMYB65 protein was located in the nucleus and cytoplasm,and had transactivation in yeast and tobacco leaf cells.The conserved motif within 226 amino acids of the C-terminal of LoMYB65 contributed to its transactivation.Overexpression of LoMYB65 caused dwarf phenotype,unnormal tapetum development,less seeds of siliques in transgenic Arabidopsis plants,the transgenic plants showed partly male sterile.Simultaneously,silencing of LoMYB65 with VIGS(Virus Induced Gene Silencing)in lily anthers caused unnormal pollen development and reduced the pollen amount.Overexpression of LoMYB65 in Arabidopsis and silencing of LoMYB65 in lily resulted in decreased pollen counts,so we speculate that LoMYB65 may be dose-dependent.Overall,these findings suggest that LoMYB65 may play an important role in anther development and pollen formation in lily.LoMYB65 may provide a useful candidate gene for pollenless breeding of lily.

A dynamic regulation of nitrogen on floret primordia development in wheat

Nitrogen(N)fertilization is critical for spike and floret development,which affects the number of fertile florets per spike(NFFs).However,the physiological regulation of the floret development process by N fertilization is largely unknown.A high temporal-resolution investigation of floret primordia number and morphology,dry matter,and N availability was conducted under three N fertilization levels:0(N0),120(N1)and 240(N2)kg ha^(−1).Interestingly,fertile florets at anthesis stage were determined by those floret primordia with meiotic ability at booting stage:meiotic ability was a threshold that predicted whether a floret primordium became fertile or abortive florets.Because the developmental rate of the 4th floret primordium in the central spikelet was accelerated and then they acquired meiotic ability,the NFFs increased gradually as N application increased,but the increase range decreased under N2.There were no differences in spike N concentration among treatments,but leaf N concentration was increased in the N1 and N2 treatments.Correspondingly,dry matter accumulation and N content of the leaf and spike in the N1 and N2 treatments was increased as compared to N0.Clearly,optimal N fertilization increased leaf N availability and transport of assimilates to spikes,and allowed more floret primordia to acquire meiotic ability and become fertile florets,finally increasing NFFs.There was no difference in leaf N concentration between N1 and N2 treatment,whereas soil N concentration at 0–60 cm soil layers was higher in N2 than in N1 treatment,implying that there was still some N fertilization that remained unused.Therefore,improving the leaf’s ability to further use N fertilizer is vital for greater NFFs.

Maternal sleep deprivation disrupts glutamate metabolism in offspring rats

Maternal sleep deprivation(MSD)has emerged as a significant public health concern,yet its effects on offspring metabolism remain poorly understood.This study investigated the metabolomic implications of MSD on offspring cognitive development,with a particular focus on alterations in glutamate metabolism.Pregnant rats were subjected to sleep deprivation during late gestation.Plasma and brain samples from their offspring were collected at different postnatal days(P1,P7,P14,and P56)and analyzed using untargeted metabolomics with liquid chromatography-mass spectrometry.Metabolomic analysis revealed significant differences in various amino acids,including L-glutamate,L-phenylalanine,L-tyrosine,and L-tryptophan,which are crucial for cognitive function.Subsequent differential analysis and partial least squares discriminant analysis(sPLS-DA)demonstrated a gradual reduction in these metabolic differences in the brain as the offspring underwent growth and development.KEGG pathway analysis revealed differential regulation of several pathways,including alanine,aspartate,and glutamate metabolism,glutathione metabolism,arginine biosynthesis,aminoacyl-tRNA biosynthesis,histidine metabolism,and taurine and hypotaurine metabolism,at different developmental stages.Mantel and Spearman analyses indicated that the observed changes in metabolites in MSD progeny may be related to various gut microbes,Ruminococcus_1,Ruminococcaceae_UCG-005,and Eubacterium_coprostanoligenes_group.Biochemical assays further demonstrated developmental changes in the L-glutamate metabolic pathway.Collectively,these findings suggest that MSD not only affects maternal wellbeing but also has enduring metabolic consequences for offspring,particularly impacting pathways linked to cognitive function.This highlights the importance of addressing maternal sleep health to mitigate potential long-term consequences for offspring.

Effects of dexmedetomidine on developmental damage of hippocampal neurons in offspring rats induced by sevoflurane inhalation anesthesia during pregnancy

Objective:To investigate the effects of developmental damage of hippocampal neurons in offspring rats induced by sevoflurane inhalation anesthesia during pregnancy and its related mechanisms.Methods:Eighteen pregnant female Sprague-Dawley(SD)rats were randomly divided into three experimental groups:the control group(intraperitoneal injection of 0.9%sodium chloride solution 100 mL),the sevoflurane inhalation anesthesia group(inhalation of 1 MAC sevoflurane for 6 h and intraperitoneal injection of 0.9%sodium chloride solution 100 mL),and the dexmedetomidine combined with sevoflurane inhalation anesthesia group(inhalation of 1 MAC sevoflurane for 6 h and intraperitoneal injection of dexmedetomidine 100 mL),with 6 rats in each group.On the day of birth,the offspring rats of each experimental group were randomly selected.And blood gas analysis was performed with left ventricular artery blood of each offspring.The expression of cleaved-caspase-3 in hippocampal neurons was measured by Western blot.The mRNA expressions of growth-associated protein-43(GAP-43)and neuronal nitric oxide synthase(nNOS)in hippocampus of offspring rats were detected by real-time RT-PCR.The protein expressions of GAP-43 and nNOS were tested by immunohistochemistry and Western blot.Results:Compared with the control group,cleaved-caspase-3 expression in hippocampal neurons of offspring rats in sevoflurane inhalation anesthesia group increased significantly.Cleaved-caspase-3 in hippocampal neurons of offspring after dexmedetomidine combined with sevoflurane inhalation anesthesia was dramatically lower than that in sevoflurane inhalation anesthesia group.Compared with the sevoflurane inhalation anesthesia group,dexmedetomidine combined with sevoflurane inhalation anesthesia could markedly up-regulate the mRNA and protein expressions of GAP-43 and nNOS.Conclusion:Dexmedetomidine can protect hippocampal neurons from developmental damage induced by sevoflurane inhalation anesthesia during pregnancy,which may be related to the up-regulation of the mRNA and protein expressions GAP-43 and nNOS.

Conventional Geothermal Systems and Unconventional Geothermal Developments: An Overview

This paper provides an overview of conventional geothermal systems and unconventional geothermal developments as a common reference is needed for discussions between energy professionals. Conventional geothermal systems have the heat, permeability and fluid, requiring only drilling down to °C, normal heat flow or decaying radiogenic granite as heat sources, and used in district heating. Medium-temperature (MT) 100°C - 190°C, and high-temperature (HT) 190°C - 374°C resources are mostly at plate boundaries, with volcanic intrusive heat source, used mostly for electricity generation. Single well capacities are °C - 500°C) and a range of depths (1 m to 20 Km), but lack permeability or fluid, thus requiring stimulations for heat extraction by conduction. HVAC is 1 - 2 m deep and shallow geothermal down to 500 m in wells, both capturing °C, with °C are either advanced by geothermal developers at <7 Km depth (Enhanced Geothermal Systems (EGS), drilling below brittle-ductile transition zones and under geothermal fields), or by the Oil & Gas industry (Advanced Geothermal Systems, heat recovery from hydrocarbon wells or reservoirs, Superhot Rock Geothermal, and millimeter-wave drilling down to 20 Km). Their primary aim is electricity generation, relying on closed-loops, but EGS uses fractures for heat exchange with earthquake risks during fracking. Unconventional approaches could be everywhere, with shallow geothermal already functional. The deeper and hotter unconventional alternatives are still experimental, overcoming costs and technological challenges to become fully commercial. Meanwhile, the conventional geothermal resources remain the most proven opportunities for investments and development.

Development and technology status of energy storage in depleted gas reservoirs

Utilizing energy storage in depleted oil and gas reservoirs can improve productivity while reducing power costs and is one of the best ways to achieve synergistic development of"Carbon Peak–Carbon Neutral"and"Underground Resource Utiliza-tion".Starting from the development of Compressed Air Energy Storage(CAES)technology,the site selection of CAES in depleted gas and oil reservoirs,the evolution mechanism of reservoir dynamic sealing,and the high-flow CAES and injection technology are summarized.It focuses on analyzing the characteristics,key equipment,reservoir construction,application scenarios and cost analysis of CAES projects,and sorting out the technical key points and existing difficulties.The devel-opment trend of CAES technology is proposed,and the future development path is scrutinized to provide reference for the research of CAES projects in depleted oil and gas reservoirs.

BMPRⅡ^(+)neural precursor cells isolated and characterized from organotypic neurospheres:an in vitro model of human fetal spinal cord development

Roof plate secretion of bone morphogenetic proteins(BMPs)directs the cellular fate of sensory neurons during spinal cord development,including the formation of the ascending sensory columns,though their biology is not well understood.Type-ⅡBMP receptor(BMPRⅡ),the cognate receptor,is expressed by neural precursor cells during embryogenesis;however,an in vitro method of enriching BMPRⅡ^(+)human neural precursor cells(hNPCs)from the fetal spinal cord is absent.Immunofluorescence was undertaken on intact second-trimester human fetal spinal cord using antibodies to BMPRⅡand leukemia inhibitory factor(LIF).Regions of highest BMPRⅡ^(+)immunofluorescence localized to sensory columns.Parenchymal and meningeal-associated BMPRⅡ^(+)vascular cells were identified in both intact fetal spinal cord and cortex by co-positivity with vascular lineage markers,CD34/CD39.LIF immunostaining identified a population of somas concentrated in dorsal and ventral horn interneurons,mirroring the expression of LIF receptor/CD118.A combination of LIF supplementation and high-density culture maintained culture growth beyond 10 passages,while synergistically increasing the proportion of neurospheres with a stratified,cytoarchitecture.These neurospheres were characterized by BMPRⅡ^(+)/MAP2ab^(+/–)/βⅢ-tubulin^(+)/nestin^(–)/vimentin^(–)/GFAP^(–)/NeuN^(–)surface hNPCs surrounding a heterogeneous core ofβⅢ-tubulin^(+)/nestin^(+)/vimentin^(+)/GFAP^(+)/MAP2ab^(–)/NeuN^(–)multipotent precursors.Dissociated cultures from tripotential neurospheres contained neuronal(βⅢ-tubulin^(+)),astrocytic(GFAP+),and oligodendrocytic(O4+)lineage cells.Fluorescence-activated cell sorting-sorted BMPRⅡ^(+)hNPCs were MAP2ab^(+/–)/βⅢ-tubulin^(+)/GFAP^(–)/O4^(–)in culture.This is the first isolation of BMPRⅡ^(+)hNPCs identified and characterized in human fetal spinal cords.Our data show that LIF combines synergistically with high-density reaggregate cultures to support the organotypic reorganization of neurospheres,characterized by surface BMPRⅡ^(+)hNPCs.Our study has provided a new methodology for an in vitro model capable of amplifying human fetal spinal cord cell numbers for>10 passages.Investigations of the role BMPRⅡplays in spinal cord development have primarily relied upon mouse and rat models,with interpolations to human development being derived through inference.Because of significant species differences between murine biology and human,including anatomical dissimilarities in central nervous system(CNS)structure,the findings made in murine models cannot be presumed to apply to human spinal cord development.For these reasons,our human in vitro model offers a novel tool to better understand neurodevelopmental pathways,including BMP signaling,as well as spinal cord injury research and testing drug therapies.

Long-term effects of gestational diabetes mellitus on the pancreas of female mouse offspring

BACKGROUND Prolonged fetal exposure to hyperglycemia may increase the risk of developing abnormal glucose metabolism and type-2 diabetes during childhood,adolescence,and adulthood;however,the mechanisms by which gestational diabetes mellitus(GDM)predisposes offspring to metabolic disorders remain unknown.AIM To quantify the nerve axons,macrophages,and vasculature in the pancreas from adult offspring born from mouse dams with GDM.METHODS GDM was induced by i.p.administration of streptozotocin(STZ)in ICR mouse dams.At 12 wk old,fasting blood glucose levels were determined in offspring.At 15 wk old,female offspring born from dams with and without GDM were sacrificed and pancreata were processed for immunohistochemistry.We quantified the density of sensory[calcitonin gene-related peptide(CGRP)]and tyrosine hydroxylase(TH)axons,blood vessels(endomucin),and macro-phages(CD68)in the splenic pancreas using confocal microscopy.RESULTS Offspring mice born from STZ-treated dams had similar body weight and blood glucose values compared to offspring born from vehicle-treated dams.However,the density of CGRP+and TH+axons,endomucin+blood vessels,and CD68+macrophages in the exocrine pancreas was significantly greater in offspring from mothers with GDM vs control offspring.Likewise,the microvasculature in the islets was significantly greater,but not the number of macrophages within the islets of offspring born from dams with GDM compared to control mice.CONCLUSION GDM induces neuronal,vascular,and inflammatory changes in the pancreas of adult progeny,which may partially explain the higher propensity for offspring of mothers with GDM to develop metabolic diseases.

FE65:a hub for neurodevelopment

FE65,initially identified as a binding partner of amyloid precursor protein(APP),is an adaptor protein enriched in the brain and regulated during development.FE65 belongs to the FE65 protein family.This family is comprised of three members,FE65,FE65 like-1(FE65L1),and FE65 like-2(FE65L2).

Constructing a standard system of city sustainable development assessment technology based on the SDGs

Given the rapid development of China’s new urbanization,cities with different locations and varying functional positioning,resource endowments,and development stages have insufficient scientific and applicable technical tools for implementing the United Nations Sustainable Development Goals(SDGs).City managers and policymakers must urgently establish SDG benchmarks to diagnose city development.Moreover,successful experiences from similar cities regarding sustainable development and self-improvement must be learned from to promote diversified,sustainable development across the country.Furthermore,emerging technologies such as artificial intelligence,the Internet of Things,big data and 5G are widely used in smart cities.Therefore,there is a growing need for“knowledge-based,personalized and intelligent”technologies to support monitoring,evaluation,and decision-making processes facilitating sustainable development in cities.This paper uses standardization as the theoretical support and technical basis.This approach can help clarify the sustainable development processes in China and clarify the evaluation results of and provide data on horizontal city comparisons,which can be used to develop evaluation technology for sustainable development in cities and construct a standardized system.The results provide a standard framework for intelligent assessment and decision-making regarding cities’sustainable development capabilities in China.Evaluating major international standardization institutions reveals that the practices of Chinese national standards should be fully absorbed and integrated to guide the evaluation of smart,resilient,and low-carbon cities.To this end,an indicator library of city sustainable development is proposed to provide standard evaluation technology methods.Finally,analyzing the response relationship of the indicator library to SDGs reveals the need for a standardized knowledge map of sustainable development assessment techniques and methods from the perspective of integrated management for sustainable development in cities.

Spatial Differentiation and Convergence Trend of High-quality Development Level of China’s Tourism Economy

This paper aims to interpret the connotation of high-quality development of tourism economy(HQTE)from the perspective of the new development concepts of innovation,coordination,green,openness and sharing,and then to evaluate the spatial differenti-ation of China’s HQTE based on provincial panel data from 2009 to 2018.Specifically,we employ the spatial convergence model to ex-plore the absolute and conditionalβconvergence trends of HQTE in the whole country and the eastern,central and western regions of China.Our empirical results reveal that:1)within the decade,from 2009 to 2018,regions of China with the highest HQTE index is its eastern region followed by the central region and then the western region,but the fastest growing one is the western region of China fol-lowed by the central region and then the eastern region.2)Whether or not the spatial effect is included,there are absolute and condition-alβconvergence in HQTE in the whole country and aforementioned three regions.3)The degree of government attention as well as the level of economic development and location accessibility are the positive driving factors for the convergence of HQTE in the whole country and the three regions.The degree of marketization and human capital have not passed the significance test either in the whole country or in the three regions.The above conclusions could deepen the understanding of the regional imbalance and spatial conver-gence characteristics of HQTE,clarify the primary development objects,and accomplish the goal of China’s HQTE.